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Andres Iniesta has insisted that nobody at Barcelona is panicking after the runaway leaders of La Liga saw their long unbeaten run come to an end.

FC Barcelona training (image Barcelona/Twitter)

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Andres Iniesta has insisted that nobody at Barcelona is panicking after the runaway leaders of La Liga saw their long unbeaten run come to an end.

Lionel Messi missed a penalty as the Catalans lost 1-0 away to local rivals Espanyol in the quarter-finals of the Copa del Rey on Wednesday, although the holders can still turn the tie around in the second leg next week.

"What nobody was expecting was that we would not lose a game until now," Iniesta told reporters while visiting a Barcelona hospital on Thursday.

It was a first defeat in 30 games in all competitions for Ernesto Valverde's side, who have still not lost in La Liga.

"It is football, it is sport, and you always have to play in very intense matches," added Iniesta, with Sunday's trip to Betis to come before the return against Espanyol.

"It is not a one-off tie and in the second leg we will try to change things. For the defeat to plant doubts would be to see it from a very negative viewpoint after so many matches without losing."

Iniesta said that he hoped to be back soon from an injury that he described as "only a strain", while Barca are also without their two record signings Philippe Coutinho and Ousmane Dembele due to thigh problems.

Dembele is out for three to four weeks after hurting himself in last week's 4-2 victory at Real Sociedad.

Betis are the great entertainers in La Liga -- their last two games have seen them win 5-3 and 3-2 -- and coach Quique Setien has urged his players to attack the leaders at the Benito Villamarin.

"Barcelona are very difficult (to play against). We will be brave, I'm sure," Setien told Cadena Ser. "It is our destiny to play, to win the ball back in the opposition half and go after them to try to pose them problems."

Faltering Real Host Depor

With Real Madrid mired in crisis, Atletico Madrid are Barcelona's nearest challengers, sitting nine points back in second place.

Diego Simeone's side entertain Girona as they seek to bounce back from a 2-1 home loss to Sevilla in the Copa del Rey.

Centre-back Diego Godin is banned but Diego Costa can return after suspension.

Valencia, a further two points back in third, will be confident of beating a Las Palmas side in wretched form -- the bottom-of-the-table side from the Canary Islands have lost their last two matches by an aggregate score of 10-0.

A 1-0 home defeat to Villarreal last weekend made it the first time Real had suffered back-to-back home league defeats in more than eight years.

They have taken just one point from their last three La Liga outings while doubts are being raised about Cristiano Ronaldo's future at the club beyond this season.

Zidane has said that he "can't imagine a Madrid without Cristiano", but the Portuguese superstar will be 33 next month and he has just four league goals this season.

Ronaldo was left out of the squad for Thursday's 1-0 Copa del Rey victory at Leganes along with Karim Benzema and Gareth Bale. They should all return against Deportivo.

"Real Madrid are Real Madrid. I don't think they are in crisis. The demand is always on them to win and so when they don't, it seems that everything is going badly. But they can beat you at any moment," warned Depor's Adrian Lopez.